Introduction
Ketamine is a sedative used for patients with extreme/refractory undifferentiated agitation
Indications for utilizing ketamine for emergent sedation of agitated patients include:
- a. Patient poses and immediate threat to patient and healthcare provider safety (RASS +4)
- b. Failure and/or futility of alternative non-pharmacologic de-escalation strategies
- c. Absence of IV access
- d. Not a candidate for intramuscular antipsychotics and/or benzodiazepines due to onset of action
Key Points
- Ketamine is a sedative option for patients with extreme or refractory undifferentiated agitation.
- Indications include an immediate safety threat (RASS +4), failed non-pharmacologic de-escalation, absent IV access, or unsuitability for IM antipsychotics/benzodiazepines.
- It achieves rapid sedation but carries risks including respiratory depression; use caution in patients with an underlying psychiatric disorder.
- Reserve ketamine for specific patient populations and as a last-line option for patient and provider safety.
Clinical Detail
Properties: Rapid acting general anesthetic producing a cataleptic-like state due to antagonism of N-methyl-D-aspartate (NMDA) receptors in the central nervous system. Ketamine also has significant analgesic/dissociative properties at lower doses.
| Property | Detail |
|---|---|
| Dose | 2–5 mg/kg IM to a max single dose of 500 mg 1–2 mg/kg IV |
| Administration | IM: Inject deep IM into large muscle (glute or vastus lateralis muscle) IV: Administer over at least 60 seconds |
| Formulation | 10 mg/mL, 50 mg/mL, 100 mg/mL *must use 100 mg/mL for IM administration to reduce volume |
| PK/PD (for amnestic effects) | Onset: 3–5 mins IM; <1 minute IV Duration: 15–25 mins IM; 5–10 minutes IV Bioavailability: 93% IM Metabolism: Extensively through hepatic N-demethylation Elimination: Greater than 90% urine, <5% feces |
| Safety | Detail |
|---|---|
| Adverse Effects | Hypertension; tachycardia; hypersalivation; nausea and vomiting; laryngospasm; emergence phenomenon during recovery phase; increased muscle function (hyperactivity, twitching, rigidity) |
| Contraindications | Significant hypertension may be hazardous, ACS, ADHF, and unstable dysrhythmia |
| Warnings & Considerations | Rapid IV administration may increase risk of respiratory depression/apnea; verify concentration of formulation; caution in diagnosed schizophrenia; hypotension in catecholamine-depleted states; pregnancy and lactation (crosses placenta) |
Evidence
| Author, Year | Design (sample size) | Intervention & Comparison | Outcome |
|---|---|---|---|
| Lin et al., 2020 | Prospective, randomized, pilot (n=93) | Ketamine 4 mg/kg IM or 1 mg/kg IV Haloperidol 5–10 mg IM/IV + lorazepam 1–2 mg IM/IV | Ketamine achieved greater sedation within 5 and 15 minutes (22% vs 0% at 5 mins; 66% vs 7% at 15 mins) |
| Mankowitz et al., 2018 | Systematic review (n=650) | Ketamine IV or IM | Mean time to sedation was 7.21 min and effective in 68.5% of patients; 30.5% of patients required intubation, but not all secondary to ketamine administration |
| Cole et al., 2016 | Prehospital prospective, observational (n=146) | Haloperidol 10 mg IM Ketamine 5 mg/kg IM | Median time to adequate sedation was faster with ketamine (5 min) vs haloperidol (17 min); intubation rates were higher with ketamine (39%) than haloperidol (4%), as well as more complications (49% vs 5%, respectively); 38% hypersalivation in ketamine group |
| Isbister et al., 2016 | Subgroup analysis from DORM II study; prospective, observational (n=49) | Ketamine as rescue treatment after droperidol alone; droperidol + DZP or MDZ; or midazolam alone | Median time to sedation post-ketamine was 20 minutes (IQR 10–30); 3 patients had adverse reactions after ketamine (vomiting n=2; desaturation n=1) |
| Riddell et al., 2016 | Prospective, observational (n=106) | Ketamine Lorazepam, midazolam, haloperidol, or benzodiazepine + haloperidol | Ketamine resulted in a greater number of patients with no agitation at 5 minutes than other medications |
| Scheppke et al., 2014 | Retrospective chart review (n=52) | Ketamine ~4 mg/kg IM *Recommended midazolam 2–2.5 mg IM or IV following ketamine for emergence reaction | 96% of patients obtained sedation, mean time to sedation was 2 minutes; 3 patients experienced significant respiratory depression; about ½ of patients received midazolam |
Trials in Progress
| Author | Status | Design | Intervention | Outcomes |
|---|---|---|---|---|
| Barbic et al. | Completed March 2020, results pending | Parallel, prospective, randomized, controlled | Ketamine 5 mg/kg IM Midazolam 5 mg IM + haloperidol 5 mg IM | Primary: Time to adequate sedation Secondary: safety and tolerability, requirement of rescue medication |
DZP = Diazepam; MDZ = Midazolam
Conclusions
- Ketamine has been shown to be effective with a quick time to sedation but is not without risks, including respiratory depression
- Used ketamine with caution in patients who have an underlying psychiatric disorder
- Ketamine should be reserved for specific patient populations and as last line for patient/provider safety
References
Ketamine. Micromedex [Electronic version].
Lin M, et al. Am J Emerg Med. 2020. https://doi.org/10.1016/
j.ajem.2020.04.013.
Mankowitz WL, et al. J Emerg Med. 2018;55(5):670-81.
Cole JB, et al. Clin Toxicol (Phila). 2016;54(7):556-562.
Isbister GK, et al. Ann Emerg Med. 2016;67(5):581-587.
Riddell J, et al. Am J Emerg Med. 2017.
http://dx.doi.org/10.1016/j.ajem.2017.02.026
Scheppke KA, et al. WestJEM. 2014;15(7);736-41.
Barbic D, et al. Trials. 2018;19(1):651. Published 2018 Nov 26.
doi:10.1186/s13063-018-2992-x
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